Leptospirosis is a paradigm for an urban slum health problem. Rapid urbanization and expanding urban poverty, together with climate, have created conditions for rat-borne transmission of the Leptospira spirochete. Epidemics occur each year in slum communities during seasonal periods of heavy rainfall and are associated with life-threatening manifestations such as acute renal failure and pulmonary hemorrhage. Interventions need to focus on prevention since case fatality is >10% despite aggressive treatment. A major barrier to identifying interventions has been the lack of prospective studies on leptospirosis. We conducted a prospective cohort investigation of 9,863 residents from a slum community in the city of Salvador. Brazil. We found that 3.6% of the community was infected each year with Leptospira. Exposures to defined infrastructure deficiencies related to open sewers and flooding were the major risk factors for infection. These findings led us to hypothesize that effective prevention of urban leptospirosis requires providing slum communities with adequate sewage and drainage systems. Furthermore, active surveillance which we conducted since 1996 identified a four-fold decline in the incidence of severe leptospirosis. This decline was unrelated to temporal variations in climate and coincided with implementation of a World Bank-funded sanitation program, which increased the coverage of the population with closed sewage systems from 26 to 68%. Improved sanitation may therefore have an impact in preventing the severe outcomes from leptospirosis. There is little information on the impact of large-scale sanitation programs in preventing infectious diseases, outside of diarrheal disease. Our findings convinced the local government to construct closed sewage systems at our cohort site and other slum communities in the periphery of Salvador. In the 1st project aim, we will perform an intervention study and prospectively determine whether a large-scale sanitation project is effective in preventing leptospirosis. We will enroll a cohort at our site and measure outcomes of Leptospira infection and disease during annual serosurveys and outpatient surveillance. In the 2nd project aim, we will identify the temporal and spatial determinants for leptospirosis in a large urban center and evaluate whether implementation of a municipal sanitation program contributed to an observed decline in severe disease incidence. We have created a large database on climate, environmental attributes and demographic and socioeconomic indicators for Salvador and will use this information to model the effect of improved sanitation on the risk for leptospirosis across time and space. We expect that the information gained from the project will lead to policy recommendations for the prevention of urban leptospirosis, which is urgently needed as the population residing in slum doubles from one to two billion in the next twenty years. Furthermore, the project's findings will likely be relevant to the control of the large number of environmentally-transmitted infectious diseases that affect impoverished urban populations. PUBLIC HEALTH RELEVANCE There is no effective prevention for leptospirosis, a severe life-threatening disease that is the cause of rat-borne epidemics among impoverished urban slum populations worldwide. The research proposed here aims to determine the impact of a large-scale sanitation project in preventing leptospirosis in a slum community in Brazil. The information gained from the project will lead to policy recommendations, which are needed to address leptospirosis in regions of the world where slum settlements are rapidly expanding.